'Alzheimer's treatment within reach after successful drug trial,' reports The Guardian as early tests on a new drug show promising signs.
The drug, verubecestat, is designed to prevent the brain making a particular protein called amyloid proteins that turns into sticky clumps of plaque.
These plaques of amyloid beta protein are found in the brains of people with Alzheimer's disease and may be a cause of mental decline.
Alzheimer's disease is the most common type of dementia, affecting an estimated 850,000 people in the UK.
Verubecestat is still in development. This early-stage trial included 32 people with mild to moderate Alzheimer's disease, who took the drug for just seven days.
The study checked whether the drug reduced amyloid proteins, and whether it had other side effects, for people who already had accumulations of the protein in the brain.
The trial raised no safety concerns about the drug, which appeared to inhibit the production of the amyloid proteins in line with the level of doses of the drug.
However, the trial did not test whether the drug affected people's symptoms of Alzheimer's disease.
Verubecestat has previously been tested on rats, rabbits, monkeys and healthy younger adults. In all these cases, it reduced levels of amyloid proteins.
Long-term (18 months to two years) studies of the drug, involving thousands of people with Alzheimer's disease, are already underway.
Once those results are in, we should know whether reducing amyloid beta actually helps prevent, slow down or reverse symptoms of Alzheimer's disease.
Verubecestat is one of a number of promising dementia drugs currently undergoing clinical trials.
Where did the story come from?
The study was carried out by researchers from Merck Research Laboratories and was funded by Merck, the drug company that makes verubecestat. It's usual for drug companies to fund research into their own drugs.
The study was published in the peer-reviewed journal, Science Translational Medicine.
Despite the overenthusiastic headline, The Guardian's news story is a balanced and accurate description of the study and the state of research into Alzheimer's disease.
The story makes it clear that the crucial question of whether the drug slows or reverses mental decline has not been answered.
The Mail Online's reporting, however, does not mention this until almost the end of the article.
What kind of research was this?
The report describes a number of studies involved in the development of verubecestat.
This includes its discovery through laboratory trials, animal studies and studies in healthy humans, before giving information about the phase 1 clinical trial in people with Alzheimer's disease.
There are three main phases of clinical trials: phases one to three.
Phase 1 trials are early-stage trials that involve a small number of people. They primarily aim to see whether a new drug is safe, tolerated and could have potential to treat a condition.
If the results are promising, these trials can then progress to later-stage trials involving more people, and comparing a drug with placebo or another treatment to better see whether the drug is safe and effective.
However, phase 1 trials can never give good evidence on whether a treatment works or not.
The phase 1 trial described in this paper aimed to test three different doses of the drug.
What did the research involve?
The report initially describes the earlier-stage development studies. Our analysis focuses on the phase 1 study in people with Alzheimer's.
After studies in animals and healthy younger adults, the researchers recruited 32 adults with mild or moderate Alzheimer's disease. Two people withdrew from the study or were found not to be eligible.
All of those who took part had fluid taken from the spine (lumbar puncture) to test for the amyloid beta and amyloid beta precursor (sAPPbeta) proteins that are characteristic of the condition.
They were divided into three groups of 10, each assigned to a different dose of verubecestat, with two patients in each group taking a placebo.
Further samples of spinal fluid were taken every three hours after dosing for 36 hours.
The participants took verubecestat or placebo each day for seven days. Researchers looked at changes in the protein levels between the groups and over time.
People were also assessed for adverse effects. This included checking vital signs like blood pressure and heart rate, taking ECG heart readings, carrying out physical and neurological assessments, and analysing blood and urine.
Previous studies of drugs to reduce amyloid beta had shown side effects on the nervous system, heart rate and liver function, so it was important to measure for signs of these problems.
Amyloid beta protein levels were measured as time-weighted averages over 24 hours to limit the effect that different dose timings might have on the results. These were expressed as percentage difference from baseline.
What were the basic results?
People who took the drug saw their amyloid beta levels drop, compared with their measurement at the start of the study:
- 57% reduction for 12mg dose
- 79% reduction for 40mg dose
- 84% reduction for 60mg dose
There were no serious adverse effects and nobody stopped taking the drug as a result of adverse effects.
The only notable adverse effects were seen in healthy volunteers taking much higher doses in a separate safety trial, not among the Alzheimer's disease patients taking daily doses up to 60mg. These included an itchy rash and a change to heart rhythm.
How did the researchers interpret the results?
The researchers say their findings have allowed them to move to the next phase of testing verubecestat: phase two and three clinical trials.
They describe the trials underway, saying: 'Given that the doses being tested in the ongoing phase 3 trials reduce CSF [cerebrospinal fluid] amyloid beta by more than 80%, and assuming that the compound continues to demonstrate an acceptable safety and tolerability profile, these trials will be able to determine whether verubecestat can be a much-needed disease-modifying treatment for Alzheimer's disease.'
They added that the trials will also help prove or disprove the theory that amyloid beta plaques cause the mental decline seen in Alzheimer's disease.
The road to the launch of a new drug treatment is long, and this latest trial represents one early step along the path.
It's encouraging that the drug did what researchers thought it would do in terms of reducing amyloid plaque in the spinal fluid, and that it didn't seem to cause serious side effects.
However, there's still a way to go before we know whether it's safe and effective for people with Alzheimer's disease.
The phase 1 trial is primarily set up to assess safety and tolerability, and get an idea of what dose to use – not to test if it works.
This phase 1 trial included just 32 people, two of whom dropped out or were excluded, who took the drug for seven days.
These developmental studies have to be carried out so researchers can learn whether it makes sense to go ahead with larger studies.
But we can't place too much weight on the results of small studies, as so many questions remain unanswered, such as:
- Does reducing amyloid beta in the spinal fluid also reduce plaques of amyloid beta in the brain?
- Does reducing amyloid beta plaques in the brain slow or reverse the mental decline seen in Alzheimer's disease?
- Does verubecestat have serious side effects that are not common enough to show up when tested on just 30 people?
The clinical trials now underway will look at thousands of people for up to two years.
The studies will look not just at what happens to people's amyloid beta levels, but what happens to their memory and thinking abilities.
The results of these trials will give a much better idea of whether the treatment is effective.
If you're concerned that you or a loved one may be showing signs of memory loss or confusion, see your GP for an assessment.
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